James Robertson and Yufeng Zhang
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Lifestyle need aerobic capacity
aerobic physical activity (APA)
◦ generates and protects new neurons,
◦ increases the volume of brain
◦ improves cognition and reduce anxiety
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positive correlation between aerobic capacity
and brain size across a wide range of
mammals
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Three times larger than expected for our
body size.
Major increase in brain size and brain size
◦ occurred during the early evolution of the genus
Homo (Figure 1)
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brain size changes in human evolution are
often interpreted in
◦ the context of cognition
◦ social complexity
◦ enhanced ecological demands on cognition
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at the same time as brain size began to
increase, aerobic activity levels
◦ long-distance trekking
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Hypothesis:
◦ human locomotor endurance had a measurable
effect on the evolution of human brain structure
and cognition
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APA leads to neurogenesis
◦ dentate gyrus of the hippocampus
◦ Gliogenesis frontal cortex
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Voluntary and forced running induce
upregulation of BDNF
Physical activity increase
◦ Insulin-like growth factor I
◦ Vascular endothelial growth factor (VEGF)
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BDNF, IGF-1 and VEGF all have important
effects on metabolic pathways
Growth factors in the periphery triggering
neurogenic action
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two hypotheses for activity-induced adult
neurogenesis:
◦ Neurotrophins and growth factors increased from
endurance activity with ancillary effects on the brain
◦ links between activity and neurogenesis may create
a neurogenic to enhance cognitive engagement
during locomotor bouts
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Intraspecific correlation
◦ BDNF
◦ IGF-1
◦ VEGF
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Interspecific correlation
◦ MMR and brain size across mammals is likely to be
related to differences in VEGF expression
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Do not clearly demonstrate evolutionary
mechanisms
Figure 2. Relationships between body size, brain size and exercise capacity.
Raichlen DA, Gordon AD (2011) Relationship between Exercise Capacity and Brain Size in Mammals. PLoS ONE 6(6):
e20601. doi:10.1371/journal.pone.0020601
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020601
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Selected for high and low MMR in rats
◦ high levels of aerobic capacity
both VEGF and
IGF-1
◦ Selective breeding for endurance running capacity
affects cognitive but not motor learning in rats
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Selectively bred for high amounts of voluntary
wheel-running
◦ higher BDNF levels
◦ larger mid-brain and dentate gyrus volumes
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Long hind-limbs
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larger canal dimensions strongly associated
with animals locomotor behaviours
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(i) intraspecific data linking aerobic capacity,
brain size, neurotrophins and growth factors;
(ii) interspecific data showing a relationship
between aerobic capacity and brain size
(iii) evolution experiments detailing how
selection for aerobic performance alone can
affect neurobiology
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Aerobic capacity linked to brain size, growth
factors
◦ Problem: What happens if you don’t “need” to run?
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Goal-oriented behaviors with high energy
costs
◦ Motivated by neurological rewards
◦ Conditions fitness enhancement
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Is there a reward-response from running?
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Endocannabinoids
◦ Released in activity-dependent manner
◦ Mesolimbic dopamine system
 eCBs relieve influence of inhibitory, GABAergic CB1 receptors
 eCBs activate dopamine (DA) neurons
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Sparling (2003) showed exercise
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eCBs may not immediately impact anxiety system
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AEA
But, rewarding the exercise effort could select for beneficial
traits
Shown in other cursorial mammals
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10 recreationally fit humans
◦ Could run for 30 min
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8 mixed breed dogs
◦ Local mongrels
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8 stupid ugly ferrets
◦ Minimal training (30 min running)
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Compared plasma AEA pre-post walk/run
◦ Stupid ferrets couldn’t walk on the treadmill
 Compared with stationary AEA
• Humans and Dogs
• Running increases
plasma AEA
• Encourage aerobic
exercise
• High intensity
necessary
• Ferrets
• Jeez ferret, get off the
couch sometime!
• Don’t you want to feel
good?!?!
• Cursorial mammals
rule!!!
Running
increases
positive
affect in
humans
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Does exercise influence anxiety via effects on
neurogenesis?
◦ BDNF – neurotrophic factor critical for plasticity and
neurogenesis
 Likely link between exercise and anti-depressive effect
◦ Previous studies in humans and animals are
problematic
 Running wheel = novel environmental stimulation
 Human exercise not standardized for subjects
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Study subjects: Homogenous group of male cyclists
(n=11)
◦ Underwent exercise test to find standardized intensity –
maximal power output (Wmax)
◦ 60 min at 55% Wmax
◦ 30 min at 75% Wmax (equivalent output condensed into
time trial for intensity)
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Blood taken: 1- at rest; 2 – 60 min; 3 – immediately
post-exercise; 4 – recovery
Tested for:
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AEA, 2-AG
AEA congeners OEA, PEA
BDNF
Beta endorphins
cortisol
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AEA and congeners increased
during exercise and recovery
2-AG did not
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Serum cortisol increased
during exercise and recovery
◦ Positively correlated with AEA
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BDNF increased during
exercise, fell during recovery
◦ Positively correlated with AEA at
end of time trial, recovery
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Beta-endorphins only
increased significantly during
intense exercise
• Rates of perceived exertion
were not correlated with eCB
levels
• RPE only correlated with
Beta-endorphin during
intense exercise
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AEA and congeners definitely affect mood
post-exercise
◦ Anti-depressant effect?
◦ What about the Beta-endorphins, could that be the
runners high?
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Is it fair to point to BDNF as the method of
influencing long term anxiety?